Crystal structure of the human p58 killer cell inhibitory receptor (KIR2DL3) specific for HLA-Cw3-related MHC class I

Background: T cells and natural killer (NK) cells perform complementary tal es in the cellular immune system. T cells identify infected cells directly through recognition of antigenic peptides that are displayed at the target cell surface by the classical major histocompatibility complex (MHC) class I molecules. NK cells monitor the target cell surface for malfunction of th is display system, lysing potentially infected cells that might otherwise e vade recognition by the T cells. Human killer cell inhibitory receptors (KI Rs) control this process by either inhibiting or activating the cytotoxic a ctivity of NK cells via specific binding to MHC class I molecules on the ta rget cell. Results: We report the crystal structure of the extracellular region of the human p58 KIR (KIR2DL3), which is specific for the human MHC class I molec ule HLA-Cw3 and related alleles. The structure shows the predicted topology of two tandem immunoglobulin-like domains, but comparison with the previou sly reported structure of the related receptor KIR2DL1 reveals an unexpecte d change of 23 degrees in the relative orientation of these domains. Conclusions: The altered orientation of the immunoglobulin-like domains mai ntains an unusually acute interdomain elbow angle, which therefore appears to be a distinctive feature of the KIRs. The putative MHC Glass I binding s ite is located on the outer surface of the elbow, spanning both domains. Th e unexpected observation that this binding site can be modulated by differe nces in the relative domain orientations has implications for the general m echanism of KIR-MHC class I complex formation.